In situ-generated chiral iron complex as efficient catalyst for enantioselective sulfoxidation using aqueous H₂O₂ as oxidant

Abstract

A series of amino alcohol-derived, Schiff-base ligands L1–L4 were synthesised and characterized. Iron complexes of these ligands [FeL1(acac)], [FeL2(acac)], [FeL3(acac)] and [FeL4(acac)] were generated in situ to catalyze the asymmetric oxidation of prochiral sulfides using aqueous H₂O₂ as a terminal oxidant. One of these complexes [FeL1(acac)] was identified as a very efficient catalyst for the enantioselective oxidation of a series of alkyl aryl sulfides with excellent enantioselectivity (75–96% ee), conversion (up to 92%) and chemo selectivity (up to 98%). During the optimization process, a series of electron-donating benzoic acid derivatives were found to favour both conversion and enantioselectivity.

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Introduction

Chiral sulfoxides are valuable compounds for their application as chiral auxiliaries,¹ ligands,² organo-catalysts³ and in pharmaceuticals.⁴ The direct and most efficient synthetic route to synthesize chiral sulfoxides was developed simultaneously by Kagan et al.⁵ and Modena et al.⁶ adapting a modified Sharpless epoxidation catalytic system. Since then there has been a spurt of activity in this area of research; various organocatalysts⁷ and metal-based catalysts have been developed,⁸ including titanium,⁹ vanadium,¹⁰ manganese,¹¹ iron,¹² aluminum,¹³ copper¹⁴ and polyoxometalate.¹⁵ Although metal-based catalysts efficiently promote asymmetric sulfoxidation reactions, the contamination of toxic metal in the product is a serious issue, especially in the synthesis of biologically active intermediates and products. Given that iron is an essential bio element, its use in various organic transformations was widely encouraged¹⁶ because of its low cost, abundance in nature and environment-friendly aspects. Recently List et al. reported the novel concept of an asymmetric counter-anion-directed catalysis (ACDC)^12t in an asymmetric sulfoxidation reaction using iron complex. This catalytic protocol provided an excellent enantioselectivity for a few substrates using PhIO as an oxidant. Asymmetric sulfoxidation protocols utilizing iron-based catalysts with hydrogen peroxide are attractive for environmental and economic reasons but also have an inherent disadvantage as iron is known to decompose H₂O₂, thereby causing catalyst destruction via hydroxyl radical generation.^12r Yet Fontecave and co-workers'^12i–12k dinuclear iron-(−)-4,5-pinene-2,2′-bipyridine complex and Bolm et al.'s^12l iron–amino alcohol-derived, Schiff-base complexes set the stage for the iron–H₂O₂ combination. Although yield and enantioselectivity were low to moderate with this protocol, a quantum improvement in the catalytic performance was observed when a catalytic amount of Li/Na salt of 4-methoxy benzoic acid was used as an additive.^12m,12n Later Katsuki et al. also reported use of the iron–salan complex with H₂O₂ (ref. 12p) in a water medium for the sulfoxidation reaction with high yield and enantioselectivity. Still, the Fe–H₂O₂ combination is under-represented for this reaction, except for a couple of reports, such as Simonneaux et al. in 2011,^12r who reported an iron-porphyrin catalyst (maximum sulfoxide enantiomeric excess [ee] 87%) and Tsogoeva et al.^12s in 2012, who reported using an in situ-generated iron complex of primary amine-derived, non-symmetrical Schiff base (with FeCl₃ as iron source) but with lower enantioselectivity (highest ee 36%). Our interest in the Fe–H₂O₂-based catalytic system is that a suitable modification in promising salen and salan ligands in combination with an appropriate iron source may provide excellent results. We have prepared a series of pentadentate salen ligands L1–L4 and used their in situ-generated iron complexes as catalysts in the enantioselective sulfoxidation of prochiral sulfides. Among these, the ligand L1 with [Fe(acac)₃] as an iron source proved to be an efficient catalytic system by providing excellent enantioselectivity up to 98% ee in the presence of 4-MeO-C₆H₄COOH as an additive.

Results and discussion

A series of pentadentate salen ligands L1–L4 were synthesized by simple condensation of commercially available bis-aldehyde (1) with different chiral amino alcohols as shown in Scheme 1. Treating these ligands with Fe(acac)₃ at appropriate M : L ratio in CH₂Cl₂, a series of Fe complexes [FeL1(acac)] to [FeL4(acac)] were generated in situ.

Scheme 1 Synthesis and structure of ligands (L1–L4).

The in situ-generated iron complexes FeL1(acac), FeL2(acac), FeL3(acac) and FeL4(acac) were applied as catalysts in asymmetric sulfoxidation reactions using methyl phenyl sulfide as a model substrate and aqueous H₂O₂ (30%) as an oxidant in CH₂Cl₂ at room temperature (25 °C ± 2). Respective data are given in Table 1. Since free iron salt itself can catalyze the oxidation of sulfide in a non-enantioselective manner (Table 1, entry 1), the ligand was taken in slight excess (1.5 equiv.) to ensure complete consumption of Fe(acac)₃. All these ligands gave moderate to high conversions and excellent selectivity (Table 1, entries 2–5), which clearly indicated that there was no beneficial oxidative kinetic resolution occurring under this reaction condition (see ESI† for details). However, among these ligands, L1 (Table 1, entry 2) was found to be better in terms of both enantioselectivity (ee, 73%) and yield (82%). Other ligands (L2, L3 and L4) with varied amino alcohols resulted in significant drops in enantioselectivity (Table 1, entries 3–5). To further investigate the effects of the iron source with the optimized ligand L1, attempts were made with [Fe(III)(dphpd)₃] (dphpd = 1,3-diphenyl-1,3-propanedionate) and FeCl₃ (Table 1, entries 6 and 7). We observed that none of these sources were better than Fe(acac)₃ in terms of conversion and enantioselectivity.

Table 1 Screening of ligands and iron source for asymmetric sulfoxidation of methyl phenyl sulfide^a

Entry	Ligand	Iron source	Conversion^b (%)	Selectivity^b (%)	ee^c (%)
a Reaction condition: methyl phenyl sulfide (0.25 mmol), Fe source (2 mol%), ligand (3 mol%), aqueous H2O2 (30%, 1.2 equiv.), in CH2Cl2 (1 ml) at room temperature for 12 h.b Conversion and selectivity were calculated by ^1H NMR analysis.c Enantiomeric excess was determined by HPLC analysis on a chiral phase Daicel Chiralcel OD column.
1	—	Fe(acac)3	21	—	—
2	L1	Fe(acac)3	82	95	73
3	L2	Fe(acac)3	75	90	40
4	L3	Fe(acac)3	67	98	18
5	L4	Fe(acac)3	55	98	20
6	L1	Fe(dphpd)3	29	99	27
7	L1	FeCl3	22	99	5

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Based on these experimental results, the ligand L1 and Fe(acac)₃ were selected as the preferred combination and thus were taken forward to optimize catalyst loading and metal-to-ligand ratio as shown in Table 2. We observed a considerable decrease in enantioselectivity when the catalyst loading (by keeping metal-to-ligand ratio at 1 : 1.5) was decreased to 1 mol% (entry 1; conversion 70%; ee 59%) from 2 mol% (entry 2; conversion 82%; ee 73%) taken in the beginning. At the same time, an increase in catalyst loading to 4 mol% was of no consequence, particularly in improving enantioselectivity (entry 3; conversion 93%; ee 72%), although there was an increase in conversion, but product selectivity dropped significantly (Table 2, entries 1–3).

Table 2 Optimization of catalyst loading and metal-to-ligand ratio with L1/Fe(acac)₃^a

Entry	Catalyst loading (mol%)	Metal : ligand	Conversion^b (%)	Selectivity^b (%)	ee^c (%)
a Reaction condition: methyl phenyl sulfide (0.25 mmol), Fe(acac)3, L1, aqueous H2O2 (30%, 1.2 equiv.), in CH2Cl2 (1 ml) at room temperature for 12 h.b Conversion and selectivity were calculated via ^1H NMR analysis.c Enantiomeric excess were determined by HPLC analysis on a chiral phase Daicel Chiralcel OD column.d H2O2 was added at once.
1	1	1 : 1.5	70	94	59
2	2	1 : 1.5	82	95	73
3	4	1 : 1.5	93	85	72
4	2	1 : 0.5	67	94	55
5	2	1 : 1.0	73	96	64
6	2	1 : 2.0	76	96	68
7^d	2	1 : 1.5	81	95	65

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Considering the structure and number of donor atoms in the ligand, the formation of bimetallic complex could not be ruled out (Scheme 2). Hence, to address this issue, UV-vis and ESI-MS spectra were recorded for the in situ-generated complexes of Fe(acac)₃ and ligand L1 in 1 : 1 and 2 : 1 ratios. The UV-vis spectra (Fig. 1) recorded for 1 : 1 metal-to-ligand ratio revealed peaks at 332, 340 and 430 nm, while the 2 : 1 ratio showed peaks at 359, 388 and 432 nm, which clearly indicates the formation of various predominant complexes.

Scheme 2 Plausible structures of the in situ-generated monomeric [FeL1(acac)] and dimeric [Fe₂L1(acac)₂] complex.

Fig. 1 UV vis. spectra of in situ-generated complex with metal-to-ligand ratio of 1 : 1 and 2 : 1.

The ESI-MS spectra (see ESI†) recorded for 1 : 1 ratio (Fig. S1†) showed a predominant peak at m/z = 558.39 attributed to monoprotonated mononuclear species [FeL1(acac) + H⁺], which matches with the calculated value 558.28 and a trace of binuclear monopositive molecular ion, that is, [Fe₂L1(acac)₂]⁺, at 711.41. On the other hand, for 2 : 1 ratio, a significant amount of binuclear species was detected in the ESI-MS spectra (Fig. S2†) along with the mononuclear complex. These mononuclear and binuclear complexes were further analyzed via high-resolution mass spectrometry. The obtained m/z for mononuclear complex [FeL1(acac)] and binuclear complex ion [Fe₂L1(acac)₂]⁺ are 557.2666 (calculated value 557.278) and 711.2378 (calculated value 711.2395), respectively, support our assumption (Fig. S3 and S4†). Interestingly, the complex prepared with 1 : 1 ratio of metal and ligand in CH₂Cl₂ or CHCl₃ on aging (>2 days) partially crystallized out L1 and the supernatant liquid showed m/z peaks arising from both bimetallic and monometallic species. Due to this behavior, optimizing the M : L ratio was prudent. It is noteworthy that in the 2 : 1 metal : ligand ratio, a significant drop in both conversion and enantioselectivity (Table 2, entry 4, conversion 67%, ee 55%) was observed, while with the 1 : 1 ratio, the conversion was almost comparable (Table 2, entry 5: conversion 73%, ee 64%). Further, the ee value was slightly less than what was obtained with 1 : 1.5 ratio. An increase in the metal-to-ligand ratio beyond 1 : 1.5, such as 1 : 2 (conversion 76%, ee 68%), was counterproductive. These experimental results (Table 2, entries 4–6) and spectral studies discussed above clearly indicate that the monometallic complex was more reactive and enantioselective than the bimetallic complex.

In continuing optimization of the reaction parameters, the effect of oxidants such as urea hydrogen peroxide (UHP) and tert butyl hydrogen peroxide (TBHP), were also tested along with 30% aqueous H₂O₂, and respective data are shown in Fig. 2. The conversion and enantioselectivity obtained for UHP were moderate, whereas TBHP as an oxidant fared poorly with this catalytic system; nevertheless, the catalyst retained high selectivity for the desired product.

Fig. 2 Effect of oxidant on enantioselective oxidation of methyl phenyl sulfide, catalyzed by in situ-generated [FeL1(acac)] complex in CH₂Cl₂ at room temperature.

Next, the effects of solvent using CH₂Cl₂, CHCl₃, CH₃OH, THF, toluene, dimethyl carbonate (DMC) and diethyl carbonate (DEC) were screened, adapting above optimized reaction conditions (Table 3). The results in CH₂Cl₂ and CHCl₃ (Table 3, entries 1 and 2) were at par, but other solvents caused a significant drop in the ee (Table 3, entries 3–5). A trial to replace the chlorinated solvent by green solvents such as DMC and DEC (Table 3, entries 6–7) failed, as these solvents gave very poor conversion and ee. Furthermore, a small increase in enantioselectivity was observed upon reducing the temperature from room temperature to 15 °C, but caused a decline in conversion (Table 3, entries 8 and 9) below 15 °C.

Table 3 Variation of solvents for asymmetric oxidation of methyl phenyl sulfide with L1/Fe(acac)₃ system^a

Entry	Solvent	Conversion^b (%)	Selectivity^b (%)	ee^c (%)
a Reaction condition: methyl phenyl sulfide (0.25 mmol), Fe(acac)3 (2 mol%), L1 (3 mol%), aqueous H2O2 (30%, 1.2 equiv.), in organic solvent (1 ml) at room temperature for 12 h.b Conversion and selectivity were calculated by ^1H NMR analysis.c Enantiomeric excess were determined by HPLC analysis on chiral phase Daicel Chiralcel columns.d The reaction was carried out at 15 °C.e The reaction was carried out at 5 °C.
1	CH2Cl2	82	95	73
2	CHCl3	75	96	70
3	CH3OH	67	98	14
4	THF	60	98	55
5	PhCH3	85	96	40
6	DMC	20	97	10
7	DEC	25	96	26
8^d	CH2Cl2	79	95	80
9^e	CH2Cl2	71	98	81

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Taking a cue from results published by Bolm et al.,^12m,12n we further tried to increase the enantioselectivity of the present system by using sub-stoichiometric amounts of electron-rich, benzoic acid derivatives as the additive. The use of p-OMeC₆H₄COOH (2 mol%) as an additive revealed its beneficial effect on conversion and enantioselectivity (conversion 91%, ee 88%) (Fig. 3). But the same additive at higher loadings beyond 2 mol% caused significant reduction in enantioselectivity. Furthermore, several other electron-rich benzoic acid derivatives and sodium salt of p-OMeC₆H₄COOH were also evaluated (Table S1†). Among these, p-OMeC₆H₄COOH was found to be ideal for conversion (91%), selectivity (95%), and ee (88%).

Fig. 3 Effect of concentration of p-OMeC₆H₄COOH as additive on enantioselective oxidation of methyl phenyl sulfide catalyzed by in situ-generated [FeL1(acac)] complex at 15 °C.

Finally, adapting 2 mol% of Fe(acac)₃, 3 mol% of ligand L1, 2 mol% p-OMeC₆H₄COOH and 1.2 equiv. of aqueous H₂O₂ in CH₂Cl₂ at 15 °C as the optimum reaction condition, we applied this catalytic protocol for the asymmetric oxidation of various prochiral alkyl aryl sulfides (Table 4). Alkyl aryl sulfides with electron-withdrawing F, Cl, and Br substituents at the para position. (Table 4, entries 2–5), meta position (Table 4, entry 8–9) and ortho position of aromatic ring (Table 4, entries 10 and 11) behaved almost the same and gave high selectivity (up to 98%) and excellent ee (91–96%), but provided low conversion with respect to unsubstituted methyl phenyl sulfide (Table 4, entry 1). Replacing an electron-withdrawing substituent at the para position via an electron-donating Me and OMe group (Table 4, entries 6 and 7) retained both conversion and ee as obtained for the representative substrate, but we noted a small reduction in selectivity (93%).

Table 4 Enantioselective oxidation of various prochiral sulfides with in situ-generated FeL1(acac)₃ complex^a

Entry	Sulfide	Conversion^b (%) (yield)	Selectivity^b (%)	ee^c (%)
a Reaction condition: sulfide (0.25 mmol), Fe(acac)3 (2 mol%), L1 (3 mol%), p-OMeC6H4COOH (2 mol%), additive (1 mol%), aqueous H2O2 (30%, 1.2 equiv.), in CH2Cl2 (1 ml) at 15 °C for 12 h.b Conversion and selectivity were calculated by ^1H NMR analysis and the values in the parentheses refer to calculated yield.c Enantiomeric excess was determined via HPLC analysis on chiral-phase Daicel Chiralcel columns.d Reaction was carried out in 0.75 mmol scale.
1		91 (86)	95	88
2		78 (76)	98	95
3		82 (80)	98	95
4		81 (79)	97	94
5		72 (69)	96	96
6		90 (86)	96	87
7		92 (86)	93	85
8		79 (77)	98	96
9		80 (78)	97	94
10		80 (76)	95	91
11		78 (73)	94	90
12		89 (87)	98	85
13		88 (85)	97	75
14^d		90 (85)	94	89

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For most of the alkyl aryl sulfides, enantioselectivity was comparable with previously reported Fe/H₂O₂-based catalytic systems (Bolm¹²ⁿ and Katsuki^12p) (Fig. 4). However, we observed a significant improvement in sulfoxide yield, and in the case of ortho-substituted substrate both yield and enantioselectivity were higher when compared to the Bolm system. But, in the case of substrates with an electron-donating group, slightly inferior results were obtained compared to the Katsuki catalytic system. Finally, we used ethyl phenyl sulfide (Table 4, entry 12) and benzyl phenyl sulfide (Table 4, entry 13) as variants for the methyl group and obtained enantioselectivity comparable to that reported by Bolm and colleagues and Katsuki and colleagues. The small decline in enantioselectivity in the case of ethyl phenyl sulfide (conversion 89%, ee 85%) and benzyl phenyl sulfide (conversion 88%, ee 75%), having bulkier ethyl and benzyl group, may be attributed to the steric effect in comparison with the methyl group. This catalytic system retained activity even at the 0.75 mmol scale (Table 4, entry 14).

Fig. 4 Structural correlation of present catalyst with previously reported iron-based catalytic systems.

Experimental

General

All solvents were dried using standard procedures, and then distilled and stored under nitrogen. NMR spectra were obtained with a Bruker-Avance-DPX-200 (200 MHz) or 500 MHz spectrometer at ambient temperature using tetramethylsilane (TMS) as the internal standard. Electronic spectra were recorded in chloroform on a Varian Cary 500 Scan UV-vis-NIR spectrophotometer, and TOFF mass of the catalysts and ligands were determined on a Micromass Q-TOF-micro instrument. Microanalysis of the ligands was carried out on a PerkinElmer 2400 CHNS analyser. Enantiomeric excess (ee) values were determined via a Shimadzu-HPLC with SPD-M10A-VP and SPD-M20A UV detector and PDR-Chiral Inc. advanced Laser Polarimeter (PDR-CLALP), using chiral Daicel Chiralcel columns with a 2-propanol/hexane mixture as eluent of the crude products.

Typical experimental procedure for enantioselective sulfoxidation reaction

A mixture of L1 (0.0075 mmol) and Fe(acac)₃ (0.005 mmol) in dry CH₂Cl₂ (1 ml), was stirred for 3 h at room temperature. After the formation of the complex, p-OMeC₆H₄COOH (0.005 mmol) was added to the reaction mixture and the stirring was continued for another 20 min. Next, an appropriate sulfide (0.25 mmol) was added to the reaction mixture, which was stirred for another 20 min. Finally the reaction mixture was cooled to 15 °C, and 1.2 equiv. of aqueous hydrogen peroxide (30%; 34 μl, 0.3 mmol) was added in 6 fractions over 40 min and the reaction mixture stirred for 12 h. Then the reaction was quenched by washing the organic layer with water (1 ml × 3). A sample of the crude reaction mixture was taken for the HPLC and NMR analysis to determine enantioselectivity, conversion and selectivity.

General methods for synthesis of ligands (L1–L4)

Chiral ligands were synthesized by the condensation reaction of readily available 4-tert-butyl-2,6-diformylphenol with chiral 2-aminoethanol derivatives by the modified procedure. The solvent for the condensation was taken depending on product solubility.

Synthesis of ligand L1. To a stirring solution of 4-tert-butyl-2,6-diformylphenol (1 mmol) in dry toluene (10 ml) under nitrogen atmosphere, (S)-(+)-tert-leucinol (1.2 mmol) solution in 2 ml dry toluene was added at room temperature under nitrogen atmosphere. After the addition of (S)-(+)-tert-leucinol, yellow precipitate of the ligand formed. The reaction mixture was then heated to 70 °C and stirred for 36 h. After complete consumption of the bis-aldehyde, yellow precipitate was filtered and washed three times with cold toluene to remove the excess (S)-(+)-tert-leucinol and dried under vacuum. Yield: 88%; m.p.: 247–249 °C; ¹H NMR (500 MHz, DMSO-D₆): δ = 14.65 (s, 1H), 8.53 (s, 2H), 7.80 (s, 2H), 4.49 (s, 2H), 3.78 (d, J = 10.5 Hz, 2H), 2.86, (d, J = 8.5 Hz, 2H), 1.29 (s, 9H), 0.92 (s, 18H); ¹³C NMR (50 MHz, DMSO-D₆): δ = 159.15, 139.73, 128.11, 120.64, 80.51, 60.45, 33.65, 32.76, 31.07; anal. calcd for C₂₄H₄₀N₂O₃ C, 71.25; H, 9.97; N, 6.92%; found C, 71.31; H, 9.89; N, 6.97%; TOF-MS (ESI⁺): m/z calcd for [C₂₄H₄₀N₂O₃] 404.30, found 405.31 [M] + H⁺.

Synthesis of ligands L2, L3 and L4. To a stirring solution of 4-tert-butyl-2,6-diformylphenol (1 mmol) in dry methanol (2 ml), (S)-(+)-valinol (1.2 mmol)/(S)-(−)-phenylalaninol (1.2 mmol)/(1R,2S)-(+)-cis-1-amino-2-indanol (1.2 mmol) in methanol (0.5 ml) was added. After adding the amino alcohol, the color of the reaction mixture changed from yellow to deep yellow, which was followed by formation of a precipitate. The reaction mixture was then stirred for 24 h. After complete consumption of 4-tert-butyl-2,6-diformylphenol (checked in TLC), the precipitate was filtered off, washed with cold hexane and finally dried in vacuum.

Ligand L2. Yellow solid; yield: 88%; m.p.: 197–199 °C; ¹H NMR (500 MHz, DMSO-D₆): δ = 14.57 (s, 1H), 8.56 (s, 2H), 7.77 (s, 2H), 4.66 (s, 2H), 3.65 (d, J = 10 Hz, 2H), 3.00 (s, 2H), 1.90 (m, 2H), 1.27, (s, 9H), 0.86 (d, J = 7 Hz, 12H); ¹³C NMR (125 MHz, DMSO-D6): δ = 159.48, 139.64, 128.42, 120.67, 76.96, 62.74, 33.67, 31.09, 29.21, 19.89, 18.00; anal. calcd for C₂₂H₃₆N₂O₃ C, 70.18; H, 9.64; N, 7.44%; found C, 70.24; H, 9.59; N, 7.48%; TOF-MS (ESI⁺): m/z calcd for [C₂₂H₃₆N₂O₃] 376.27, found 377.28 [M] + H⁺.

Ligand L3. Yellow solid; yield: 88%; m.p.: 136–138 °C; ¹H NMR (500 MHz, DMSO-D₆): δ = 14.25 (s, 1H), 8.38 (s, 2H), 7.68 (s, 2H), 7.26–7.23 (m, 4H), 7.19–7.14 (m, 6H), 4.83 (s, 2H), 3.61 (m, 2H), 3.48 (d, J = 3.5, 2H), 2.97 (dd, J = 13.5 Hz, J = 3.5 Hz, 2H), 2.79 (dd, J = 13.5 Hz, J = 8 Hz, 2H), 1.25 (s, 9H); ¹³C NMR (125 MHz, DMSO-D₆): 159.19, 139.84, 138.90, 129.35, 128.13, 125.96, 120.45, 73.01, 64.24, 38.47, 33.74, 31.13; anal. calcd for C₃₀H₃₆N₂O₃ C, 76.24; H, 7.68; N, 5.93%; found C, 76.19; H, 7.74; N, 5.87%; TOF-MS (ESI⁺): m/z calcd for [C₃₀H₃₆N₂O₃] 472.27, found 473.28 [M] + H⁺.

Ligand L4. Yellow solid; yield: 88%; m.p.: 195–197 °C; ¹H NMR (500 MHz, DMSO-D₆): δ = 14.18 (br, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 7.82 (s, 1H), 7.53 (d, J = 2.5 Hz, 1H), 7.43 (d, J = 2.5 Hz, 1H), 7.35–7.34 (m, 1H), 7.31–7.27 (m, 2H), 7.23–7.21 (m, 3H), 7.14–7.12 (m, 1H), 5.04 (br, 2H), 4.77–4.70 (m, 2H), 4.53 (q, J = 5 Hz, 2H), 3.17–307 (m, 2H), 2.99–2.89 (m, 2H), 1.27 (s, 9H); ¹³C NMR (125 MHz, DMSO-D₆): δ = 166.43, 161.38, 158.84, 142.39, 142.07, 141.81, 141.63, 141.17, 140.98, 139.17, 139.06, 128.52, 128.48, 127.99, 127.78, 126.69, 126.57, 126.46, 125.58, 124.99, 124.62, 124.62, 124.55, 124.43, 117.35, 87.28, 78.48, 74.05, 73.77, 73.20, 68.35, 33.72, 31.12; anal. calcd for C₃₀H₃₂N₂O₃ C, 76.90; H, 6.88; N, 5.98%; found C, 76.84; H, 6.93; N, 6.07%; TOF-MS (ESI⁺): m/z calcd for [C₃₀H₃₂N₂O₃] 468.24, found 469.25 [M] + H⁺.

Conclusions

In conclusion, a highly efficient iron–H₂O₂-based catalytic protocol was developed for asymmetric sulfoxidation. The simplicity of the procedure and reaction condition makes it attractive over other metal-catalyzed catalytic systems. This catalyst not only showed high enantioselectivity (up to 96%) for sterically and electronically diverse types of sulfides, but it also provided excellent chemoselectivity (up to 98%) with good conversion (up to 92%). Substrates containing electron-withdrawing substituents seemed to be less reactive, as those gave comparatively low conversion but provided slightly higher enantioselectivity and chemoselectivity even for ortho-substituted sulfides.

Acknowledgements

CSIR-CSMCRI Communication no. DIMC-015-14. We are grateful to the UGC and CSIR-Network Project on Catalysis for financial assistance, as well as to the Analytical Discipline and Centralized Instrument Facility for providing access to instruments and equipment.

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Footnote

† Electronic supplementary information (ESI) available: Characterization data of products, ¹H, ¹³C NMR spectra of products and ligands, and description of HPLC chromatograms of products. See DOI: 10.1039/c4ra09237f

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